Therapeutic Dissolution of Aberrant Phases by Nuclear-Import Receptors.

Therapeutic Dissolution of Aberrant Phases by Nuclear-Import Receptors.
Trends Cell Biol. 2019 Jan 16;:
Authors: Guo L, Fare CM, Shorter J
Abstract
Nuclear-import receptors (NIRs) bind nuclear-localization signals (NLSs) of protein cargo in the cytoplasm and transport them into the nucleus. Here, we review advances establishing that NIRs also function in the cytoplasm to prevent and reverse functional and aberrant phase transitions of their cargo, including neurodegenerative disease-linked RNA-binding proteins (RBPs) with prion-like domains, such as TDP-43, FUS, hnRNPA1, and hnRNPA2. NIRs selectively extract cargo from condensed liquid phases thereby regulating functional phase separation. Consequently, NIRs sculpt cytoplasmic membraneless organelles and regulate cellular organization beyond their canonical role in nuclear import. Elevating NIR expression dissolves cytoplasmic RBP aggregates, restores functional RBPs to the nucleus, and rescues disease-linked RBP toxicity. Thus, NIRs could be leveraged therapeutically to restore RBP homeostasis and mitigate neurodegeneration.
PMID: 30660504 [PubMed - as supplied by publisher]

Source: Trends in Cell Biology - January 16, 2019 Category: Cytology Authors: Guo L, Fare CM, Shorter J Tags: Trends Cell Biol Source Type: research